Cancer Anorexia Research Articles

DNA Methylation Signatures Characterize Gene Expression Modulation in Lung Cancer Patients Affected by Anorexia.

The pathophysiology of cancer anorexia is multifactorial and unclear. Transcriptomic analysis from PBMCs RNA showed diverse patterns of gene expression pathways in anorexic cancer patients. We assessed whether the different transcriptomic signatures are modulated by DNA methylation in lung cancer patients presenting with poor appetite. Lung cancer patients and controls were enrolled, and anorexia was assessed by the FAACT-score questionnaire. Genome-wide DNA methylation was determined by Human Infinium MethylationEPIC BeadChip Kit. Data from genome-wide methylation analysis were merged with those from gene expression analysis, previously obtained by RNA sequencing (NGS). Four groups of genes were identified for each comparison: hypermethylated repressed, hypermethylated induced, hypomethylated repressed, and hypomethylated induced. Cancer patients (n = 16) showed 382 differentially methylated genes when compared with controls (n = 8). Anorexic patients (n = 8) presented 586 hypomethylated and 174 hypermethylated genes compared with controls. In anorexic patients vs. non-anorexic (n = 8), 211 genes were identified as hypomethylated and 90 hypermethylated. When microarray methylation data were merged with transcriptomic data by RNA sequencing, we observed significant differences in anorexic patients vs. controls; a total of 42 genes resulted as hypomethylated and induced, 5 hypermethylated repressed, 10 hypermethylated induced, and 15 hypomethylated repressed. The CG sites analyzed by targeted bisulfite NGS in four genes of interest (FLNA, PGRMC1, GNL3L, and FHL1) resulting as hypomethylated in anorexic vs. controls allowed the validation of the data obtained from DNA methylation. Interestingly, the four genes resulted as hypomethylated in anorexic patients vs. non-anorexic patients and vs. controls (p < 0.0001). Our data support that methylation is implicated in cancer-associated anorexia and nutritional derangements among lung cancer patients.

Mirtazapine versus megestrol acetate in treatment of anorexia-cachexia in advanced cancer patients: a randomized, double-blind trial.

Cancer-related anorexia-cachexia comprises one of the most common syndromes of advanced cancer patients. The management of cancer-related anorexia-cachexia is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of cancer-related anorexia-cachexia. This study is considered to find out whether there is any role of mirtazapine in the improvement of anorexia in cancer patients. A total of 80 cancer-anorexia patients were enrolled. Patients in the trial arm received the standard chemotherapy medication plus one tablet of mirtazapine 15mg daily at night orally for 8weeks starting from the day of an initial assessment. The control arm received the standard chemotherapy medication plus one tablet of megestrol acetate 160mg daily orally for 8weeks starting from the day of an initial assessment. Each patient was assessed by validated versions of Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale v 4 questionnaires. After 4 and 8weeks each patient was evaluated again using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale tool. The quality of life of each patient was assessed by European Organization for Research and Treatment QLQ-C30 v 3.0. After 4 to 8weeks of treatment, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale score in cancer anorexia patients in the mirtazapine improved anorexia significantly. However, the improvement after 4 to 8weeks was not statistically significant when it was compared with the megestrol acetate (P>0.05). Therefore, the findings of this study reveal that mirtazapine might be a potential alternative to megestrol acetate, as it has shown potential efficacy as like as megestrol acetate.

Magnetic resonance imaging to assess the brain response to fasting in glioblastoma-bearing rats as a model of cancer anorexia

BackgroundGlobal energy balance is a vital process tightly regulated by the brain that frequently becomes dysregulated during the development of cancer. Glioblastoma (GBM) is one of the most investigated malignancies, but its appetite-related disorders, like anorexia/cachexia symptoms, remain poorly understood.MethodsWe performed manganese enhanced magnetic resonance imaging (MEMRI) and subsequent diffusion tensor imaging (DTI), in adult male GBM-bearing (n = 13) or control Wistar rats (n = 12). A generalized linear model approach was used to assess the effects of fasting in different brain regions involved in the regulation of the global energy metabolism: cortex, hippocampus, hypothalamus and thalamus. The regions were selected on the contralateral side in tumor-bearing animals, and on the left hemisphere in control rats. An additional DTI-only experiment was completed in two additional GBM (n = 5) or healthy cohorts (n = 6) to assess the effects of manganese infusion on diffusion measurements.ResultsMEMRI results showed lower T1 values in the cortex (p-value < 0.001) and thalamus (p-value < 0.05) of the fed ad libitum GBM animals, as compared to the control cohort, consistent with increased Mn2+ accumulation. No MEMRI-detectable differences were reported between fed or fasting rats, either in control or in the GBM group. In the MnCl2-infused cohorts, DTI studies showed no mean diffusivity (MD) variations from the fed to the fasted state in any animal cohort. However, the DTI-only set of acquisitions yielded remarkably decreased MD values after fasting only in the healthy control rats (p-value < 0.001), and in all regions, but thalamus, of GBM compared to control animals in the fed state (p-value < 0.01). Fractional anisotropy (FA) decreased in tumor-bearing rats due to the infiltrate nature of the tumor, which was detected in both diffusion sets, with (p-value < 0.01) and without Mn2+ administration (p-value < 0.001).ConclusionsOur results revealed that an altered physiological brain response to fasting occurred in hunger related regions in GBM animals, detectable with DTI, but not with MEMRI acquisitions. Furthermore, the present results showed that Mn2+ induces neurotoxic inflammation, which interferes with diffusion MRI to detect appetite-induced responses through MD changes.

The GDF15-GFRAL axis mediates chemotherapy-induced fatigue in mice

Cancer-related fatigue is defined as a distressing persistent subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning. This form of fatigue is highly prevalent during cancer treatment and in some patients, it can persist for years after treatment has ended. An understanding of the mechanisms that drive cancer-related fatigue is still lacking, which hampers the identification of effective treatment options. Various chemotherapeutic agents including cisplatin are known to induce mitochondrial dysfunction and this effect is known to mediate chemotherapy-induced peripheral neuropathy and cognitive dysfunction. Mitochondrial dysfunction results in the release of mitokines that act locally and at distance to promote metabolic and behavioral adjustments to this form of cellular stress. One of these mitokines, growth differentiation factor 15 (GDF15) and its receptor, glial cell line-derived neurotrophic factor family receptor α–like (GFRAL), have received special attention in oncology as activation of GFRAL mediates the anorexic response that is responsible for cancer anorexia. The present study was initiated to determine whether GDF15 and GFRAL are involved in cisplatin-induced fatigue. We first tested the ability of cisplatin to increase circulating GDF15 in mice before assessing whether GDF15 can induce behavioral fatigue measured by decreased wheel running in healthy mice and increase behavioral fatigue induced by cisplatin. Mice administered a long acting form of GDF15, mGDF15-fc, decreased their voluntary wheel running activity. When the same treatment was administered to mice receiving cisplatin, it increased the amplitude and duration of cisplatin-induced decrease in wheel running. To determine whether endogenous GDF15 mediates the behavioral fatigue induced by cisplatin, we then administered a neutralizing monoclonal antibody to GFRAL to mice injected with cisplatin. The GFRAL neutralizing antibody mostly prevented cisplatin-induced decrease in wheel running and accelerated recovery. Taken together these findings demonstrate for the first time the role of the GDF15/GFRAL axis in cisplatin-induced behaviors and indicate that this axis could be a promising therapeutic target for the treatment of cancer-related fatigue.

Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia.

Cancer cachexia syndrome is a major cause of morbidity and mortality in cancer patients in the advanced stage. It is a devastating disorder characterized by nutritional impairment, weakness, and wasting, and it affects treatment success and quality of life. Two major symptoms of cancer cachexia are anorexia and weight loss. Weight loss in cachexia is not reversed through increased food intake, suggesting that anorexia and weight loss in cancer patients are regulated by independent molecular mechanisms. Although the wasting phenotype mostly occurs in skeletal muscle and adipose tissue, other organs, such as the brain, liver, pancreas, heart, and gut, are also involved in cachexia. Thus, cachexia is a multiorgan syndrome. Although the molecular basis of cancer cachexia-induced weight loss is known, the mechanism underlying anorexia is poorly understood. Here, we highlight our recent discovery of a new anorexia mechanism by which a tumor-derived humoral factor induces cancer anorexia by regulating feeding-related neuropeptide hormones in the brain. Furthermore, we elucidated the process through which anorexia precedes tissue wasting in cachexia. This review article aims to provide an overview of the key molecular mechanisms of anorexia and tissue wasting caused by cancer cachexia.

Assessment and nonpharmacological management for patients with cancer anorexia-cachexia syndrome: a best practice implementation project.

Cancer anorexia-cachexia syndrome (CACS) is a common multifactorial syndrome, which affects up to 80% patients with advanced cancer. At present, evidence to support the benefit of pharmacological intervention in the management of CACS is limited. Patients would benefit from standard procedures for early assessment and identification of cancer anorexia-cachexia, and using nonpharmacological strategies to manage patients with CACS. This best practice implementation project aimed to implement an evidence-based practice in assessing and managing patients with CACS, thereby improving the compliance of clinical practice with the best evidence and the quality of life of patients with CACS. This was an evidence-based audit and feedback project that used a three-phase approach at a public hospital in China. Phase 1 included the development of seven evidence-based audit criteria and carrying out a baseline audit on 30 patients using the JBI's Practical Application of Clinical Evidence System in the Department of Radiation Oncology of Nanfang Hospital. Phase 2 utilized the Getting Research into Practice component of the Practical Application of Clinical Evidence System to identify barriers to compliance with best practice principles and developed strategies and resources to improve compliance. Phase 3 involved conducting a follow-up audit using the same sample size and audit criteria to assess the results of interventions implemented to improve practice and identify issues that would be addressed in future audit. The compliance rates of audit criteria 1, 2 and 6 were 100% at both baseline and follow-up audit. After the application of evidence, the compliance rate increased from 0 to 100% for audit criterion 3, from 0 to 76.6% for audit criterion 4, from 23 to 70% for audit criterion 5, and from 0 to 40% for audit criterion 5. The best evidence for the assessment and nonpharmacological management of cancer patients with CACS can improve clinical practice, the quality of clinical nursing, and patient satisfaction. The application of electronic informatization promotes the implementation and maintenance of best practice.

Cannabinoid use for appetite stimulation and weight gain in cancer care: Does recent evidence support an update of the European Society for Clinical Nutrition and Metabolism clinical guidelines?

Cannabinoids have been used medicinally for thousands of years. Clinical trials support their use for treatment of chemotherapy-induced nausea and vomiting and HIV- and AIDS-related anorexia. Cancer anorexia cachexia syndrome (CACS) is a common debilitating condition and is associated with poor prognosis. The 2016 European Society for Parenteral and Enteral Nutrition clinical guidelines on nutrition in cancer patients concluded that "there are insufficient consistent clinical data to recommend cannabinoids to improve taste disorders or anorexia in cancer patients." The increased attention that cannabinoids have received in recent years warrants an updated evaluation of the literature on this topic, as practitioners are likely to encounter cancer patients interested in cannabinoid use. A systematic literature search was performed to assess the current body of evidence concerning cannabinoid use for the stimulation of appetite and oral intake by cancer patients. Over the past 20 years, 6 randomized controlled trials have evaluated the impact of cannabinoids on appetite-related outcomes in oncology patients in comparison with a control group or placebo. Based on this literature, cannabinoids do not appear to improve appetite, oral intake, weight, chemosensory function, or appetite-related quality of life. Limitations of the literature include small sample sizes, lack of adjustment for confounding variables, and difficulties conducting true placebo-controlled trials with a drug that may result in psychoactive side effects. Further exploration of the impact of cannabinoid use on CACS by using large, well-designed clinical trials is needed.

Cancer-associated anorexia: Validity and performance overtime of different appetite tools among patients at their first cancer diagnosis

Anorexia is a frequent symptom in cancer and we aimed to assess its prevalence among patients at their first cancer diagnosis by different appetite tools and the relationship between each tool with self-reports of food intake. We also tested whether cancer anorexia influences outcomes independently of reduced food intake or body weight loss (BWL) overtime and whether BWL was associated with complications during anticancer-therapy. Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score, self-assessment of appetite, Anorexia Questionnaire (AQ) and Visual Analog Scale (VAS) were administered. Percent of food intake was used as a criterion measure of anorexia. We registered BWL and anticancer-therapy complications over 3-month-follow-up. 438 cancer patients from 7 cancer-centers worldwide were included. The prevalence of anorexia was 39.9% by FAACT score, 40.2% by VAS, 40.6% by the self-assessment of appetite and 65.4% by AQ. Low food intake (≤50%) was reported in 28% of patients. All appetite tools correlated with food intake percent (P<0.0001). We documented a correlation between self-assessment of appetite, FAACT score, VAS and BWL overtime (P<0.04). The self-assessment of appetite (P=0.0152) and the FAACT score (P=0.043) were associated with BWL independently of anticancer therapies. Among patients with BWL, the risk to develop complications was greater with respect to those who maintained a stable or gained body weight (P=0.03). In our sample of cancer patients, FAACT score and self-assessment of appetite performed well when low food intake was used as a criterion measure, and revealed an association of anorexia with BWL, which was, in turn, related to the development of anticancer-therapy complications.

Tumour-derived Dilp8/INSL3 induces cancer anorexia by regulating feeding neuropeptides via Lgr3/8 in the brain.

In patients with advanced-stage cancer, cancer-associated anorexia affects treatment success and patient survival. However, the underlying mechanism is poorly understood. Here, we show that Dilp8, a Drosophila homologue of mammalian insulin-like 3 peptide (INSL3), is secreted from tumour tissues and induces anorexia through the Lgr3 receptor in the brain. Activated Dilp8-Lgr3 signalling upregulated anorexigenic nucleobinding 1 (NUCB1) and downregulated orexigenic short neuropeptide F (sNPF) and NPF expression in the brain. In the cancer condition, the protein expression of Lgr3 and NUCB1 was significantly upregulated in neurons expressing sNPF and NPF. INSL3 levels were increased in tumour-implanted mice and INSL3-treated mouse hypothalamic cells showed Nucb2 upregulation and Npy downregulation. Food consumption was significantly reduced in intracerebrospinal INSL3-injected mice. In patients with pancreatic cancer, higher serum INSL3 levels increased anorexia. These results indicate that tumour-derived Dilp8/INSL3 induces cancer anorexia by regulating feeding hormones through the Lgr3/Lgr8 receptor in Drosophila and mammals.

A randomised, double blind, placebo-controlled trial of megestrol acetate or dexamethasone in treating symptomatic anorexia in people with advanced cancer

This multi-site, double blind, parallel arm, fixed dose, randomised placebo controlled phase III study compared megestrol acetate 480 mg/day with dexamethasone 4 mg/day for their net effects on appetite in people with cancer anorexia. Patients with advanced cancer and anorexia for ≥ 2 weeks with a score ≤ 4 (0–10 numeric rating scale (NRS) 0 = no appetite, 10 = best possible appetite) were recruited. Participants received megestrol 480 mg or dexamethasone 4 mg or placebo daily for up to 4 weeks. Primary outcomes were at day 7. Responders were defined as having a ≥ 25% improvement in NRS over baseline. There were 190 people randomised (megestrol acetate n = 61; dexamethasone n = 67, placebo n = 62). At week 1 (primary endpoint), 79·3% in the megestrol group, 65·5% in the dexamethasone group and 58·5% in the placebo group (p = 0.067) were responders. No differences in performance status or quality of life were reported. Treatment emergent adverse events were frequent (90·4% of participants), and included altered mood and insomnia. Hyperglycemia and deep vein thromboses were more frequent when on dexamethasone than the other two arms. There was no difference in groups between the three arms, with no benefit seen over placebo with anorexia improving in all arms.Trail registration: The trial was registered on 19/08/2008 with the Australian New Zealand Clinical Trials Registry (ACTRN12608000405314).

Megestrol acetate in cancer cachexia and anorexia: Tertiary care experience

Megestrol acetate in cancer cachexia and anorexia: Tertiary care experience

Virtual Teaming: Leveraging Team Science Sense-Making During COVID-19.

Individuals with cancer anorexia cachexia syndrome (CACS) experience multifaceted distress. To address CACS patient concerns regarding their experience of care, our cancer center established a specialized CACS clinic in 2016. We applied the team science principle of the team mental model (TMM) to support development of an effective interprofessional collaborative CACS care team. In 2020, cessation of CACS clinic in-person visits during coronavirus disease 2019 (COVID-19) threatened the viability of the entrenched TMM and once again jeopardized the patient experience of care.We present a case-based vignette as a representative composite of patient experiences to illustrate the challenges. A 48-year-old female was referred to our CACS clinic for pancreatic cancer-associated appetite and weight loss during COVID-19. To reduce risk of infection, in-person clinic visits were curtailed. When informed about the resulting need to defer the CACS assessment, the patient and her spouse expressed concern that postponement would adversely affect her ability to undergo anticancer treatments or achieve beneficial outcomes.To minimize delays in CACS treatment and optimize the patient experience of care, we applied the team science principle of sense-making to help the team rapidly reformulate the TMM to provide interprofessional collaborative CACS care via telemedicine. The sense-making initiative highlights opportunities to examine sense-making within health care teams more broadly during and after the pandemic. The application of sense-making within interprofessional cancer care teams has not been described previously.

Association between Growth Differentiation Factor-15 (GDF-15) Serum Levels, Anorexia and Low Muscle Mass among Cancer Patients.

Simple SummaryIn our study, the novel inflammatory cytokine Growth Differentiation Factor-15 (GDF-15) has been found elevated in patients with gastrointestinal and lung cancer and associated with anorexia. Patients with gastrointestinal cancer were found more anorexic (based on the FAACT score) and showed higher GDF-15 serum levels than patients with lung cancer. We also evaluated the muscularity status of the patients by CT scan. No difference was found in GDF-15 levels between cancer patients with low muscle mass vs. those with moderate/high muscularity and between patients with body weight loss vs. those with stable weight. Based on our observations, we confirm the role of GDF-15 in the pathogenesis of anorexia in cancer, although the mechanisms of action of this cytokine in cancer should be further unveiled also regarding its potential involvement in changes in muscularity.The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity.

Anorexia-cachexia syndrome in cancer patients: pathogenetic aspects and treatment options

Background. Modern standards for the treatment of both solid tumors and tumors of the blood system provide a mandatory assessment of the objective status of the patient. One of the important criteria of which is nutritional status. Underestimating the role of nutritional support in the treatment of cancer patients leads to a deterioration of treatment results due to the progressive deterioration of nutritional status and the development of cancer anorexia cachexia syndrome (CACS), which is an independent adverse factor leading to the death of the patient. The increase in the number of cancer patients with risk factors for CACS development requires not only close attention of clinicians to this problem, but also the development of clear recommendations for the diagnosis and management of such patients. This can contribute to solving several problems at once. First, it will allow optimizing monitoring of cancer patients predisposed to CACS development during anticancer treatment. Secondly, it will provide an opportunity to develop a diagnostic algorithm to prevent it. Third, the use of the identified criteria for predicting and outcome of complications both on an outpatient basis and in a hospital will be aimed at creating favorable conditions for anticancer therapy and thereby improving long-term treatment results and patients quality of life. Studying the mechanisms of development of CACS, the possibilities of correcting this condition, indicate the need for a multimodal concept and the rejection of the search for a “magic pill”. The results of a multicenter, prospective randomized study conducted in the oncology and hematology departments of healthcare institutions.Objective: to evaluate the effectiveness of FortiCare oral nutritional support in cancer patients under the real clinical practice.Materials and methods. The study included 96 patients with stage II–IV tumors. Radiation therapy was received by 28 patients, chemotherapy ‒ by 68 patients. Patient information was collected using an individual registration card. The patients were randomized according to nutritional support tactics (1:1). In the study group, with radiation (n = 14) and chemotherapy (n = 34), patients received enteral nutrition Forticare orally 125 ml 3 times a day in parallel with their usual diet. Patients in the control group during radiation therapy (n = 14) received the required amount of calories from their usual diet. During chemotherapy, patients in the control group (n = 34) with a lack of daily calorie intake received additional parenteral nutrition.Results and conclusion. While taking FortiCare, there was a smaller loss of body weight (p ≤0.05), a frequency of mucositis of the oral cavity, and esophagitis (p &gt;0.05). With chemotherapy, the incidence of diarrhea (p &lt;0.001) and constipation (p &lt;0.05) was detected less frequently than in the control group. A decrease in the frequency of hematological toxicity (leukopenia, thrombocytopenia) was noted (p &gt;0.05).

Plasma enterobacterial ClpB levels and ClpB- and α-MSH–reactive immunoglobulins in lung cancer patients with and without anorexia

Anorexia represents a common and debilitating clinical problem in patients with several forms of cancer, in particular lung cancer, but its mechanisms are not completely understood. Recently, the caseinolytic-protease-B (ClpB) homologue protein, produced by common gut bacteria, such as Escherichia coli, was identified as an antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. ClpB was previously detected in human plasma and displayed satietogenic properties; however, its possible relevance to cancer anorexia has not yet been investigated. To address this question, we analyzed plasma ClpB concentrations as well as levels and affinities of anti-ClpB andα-MSH-reactive antibodies in patients with lung cancer with and without anorexia as compared with body mass index-matched healthy controls with normal appetite. We found that plasma ClpB concentrations were significantly lower in non-anorexic patients with cancer than those of the control group (P=0.028). In contrast, patients with cancer and anorexia had lower levels of anti-ClpB immunoglobulins (Ig)M (P < 0.0001) and of both α-MSH IgM and IgG (P < 0.05) with respect to controls. Moreover, in patients with cancer and anorexia, anti-ClpB IgG showed a trend of lower affinities compared with non-anorexic patients (P=0.05). Taken together, the results revealed a reduced humoral immune response to ClpB in patients with cancer and anorexia, which may lead to an enhanced satietogenic effect of this enterobacterial protein contributing to the mechanisms of reduced appetite.

Asprosin is associated with anorexia and body fat mass in cancer patients.

Increasing evidence suggests that many adipokines are involved in cancer-related anorexia and cachexia syndrome (CACS), although the underlying mechanism remains to be clarify. Asprosin is a new peptide hormone mainly secreted by white adipose tissues that can increase appetite and body weight. In this cross-sectional study, we tested whether asprosin may intervene in the development of CACS. The fasting plasma asprosin levels were determined via enzyme-linked immune-sorbent assay. Anorexia was determined using the anorexia/cachexia subscale (A/CS) of the functional assessment of anorexia/cachexia therapy (FAACT) questionnaire. The body composition was assessed using bioelectrical impedance analysis. The association of plasma asprosin with anorexia, cachexia, and nutritional status was analyzed. One hundred twenty treatment-naïve patients with pathological confirmed gastrointestinal or lung cancer and 14 mild gastritis patients were recruited. We found no significant difference in asprosin levels between subgroups of patients by age, sex, cancer types or stage. Correlation analysis suggested that asprosin levels were positively associated with body fat mass (r = 0.248, p = 0.043). No correlations were found between asprosin levels and hemoglobin, white blood cell count, blood platelet count, albumin, C-reactive protein, glucose, cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, body mass index, body fat percentage, protein, skeletal muscle, muscle mass, lean body mass, and basal metabolic rate. Furthermore, asprosin levels were not significantly different between patients with or without cachexia. However, patients with anorexia had significantly lower asprosin levels compared with patients without anorexia. No significant difference in asprosin levels between gastritis and gastric cancer patients. Similarly, no significant change of asprosin levels occurred postoperatively in 10 gastric cancer patients. Patients with anorexia had significantly lower asprosin levels compared with patients without anorexia. We therefore speculated that asprosin might intervene in the development of cancer anorexia and serve as a potential therapeutic target.

Ketone Bodies Attenuate Wasting in Models of Atrophy.

BackgroundCancer Anorexia Cachexia Syndrome (CACS) is a distinct atrophy disease negatively influencing multiple aspects of clinical care and patient quality of life. Although it directly causes 20% of all cancer‐related deaths, there are currently no model systems that encompass the entire multifaceted syndrome, nor are there any effective therapeutic treatments.MethodsA novel model of systemic metastasis was evaluated for the comprehensive CACS (metastasis, skeletal muscle and adipose tissue wasting, inflammation, anorexia, anemia, elevated protein breakdown, hypoalbuminemia, and metabolic derangement) in both males and females. Ex vivo skeletal muscle analysis was utilized to determine ubiquitin proteasome degradation pathway activation. A novel ketone diester (R/S 1,3‐Butanediol Acetoacetate Diester) was assessed in multifaceted catabolic environments to determine anti‐atrophy efficacy.ResultsHere, we show that the VM‐M3 mouse model of systemic metastasis demonstrates a novel, immunocompetent, logistically feasible, repeatable phenotype with progressive tumor growth, spontaneous metastatic spread, and the full multifaceted CACS with sex dimorphisms across tissue wasting. We also demonstrate that the ubiquitin proteasome degradation pathway was significantly upregulated in association with reduced insulin‐like growth factor‐1/insulin and increased FOXO3a activation, but not tumor necrosis factor‐α‐induced nuclear factor‐kappa B activation, driving skeletal muscle atrophy. Additionally, we show that R/S 1,3‐Butanediol Acetoacetate Diester administration shifted systemic metabolism, attenuated tumor burden indices, reduced atrophy/catabolism and mitigated comorbid symptoms in both CACS and cancer‐independent atrophy environments.ConclusionsOur findings suggest the ketone diester attenuates multifactorial CACS skeletal muscle atrophy and inflammation‐induced catabolism, demonstrating anti‐catabolic effects of ketone bodies in multifactorial atrophy.

Editorial introductions

Editorial introductions

Corresponding Application of quality control circle in reducing the incidence of moderate or severe malnutrition in gastric cancer patients under chemotherapy

Objective To explore the effect of quality control circle(QCC)on reducing the incidence of moderate or severe malnutrition in gastric cancer patients under chemotherapy. Methods Before the activity (February to March 2016), 146 gastric cancer patients under chemotherapy were selected as the control group, and regular nutrition nursing (dietary guidance and regular nutrition-related health lectures) was given. After the activity (February to March 2017), 139 gastric cancer patients under chemotherapy were selected as QCC group, and the standard intervention of quality control circle was implemented. The nutritional status of patients before and after improvement was compared. Results After finding the cause and formulating and implementing the measures, the 24-hour consultation rate, the incomplete remission rate of nausea/vomiting, the incidence of cancer anorexia, and the rate of missed visits in QCC group were significantly different with those in control group (P<0.05). The incidence of moderate or severe malnutrition was 16.55% in QCC group and 65.07% in control group, and the difference was statistically significant (P<0.01). Conclusions The quality control circle activity can effectively reduce the incidence of moderate or severe malnutrition and improve the quality of life in gastric cancer patients under chemotherapy. It can also improve the self-discipline and initiative of medical staff and improve the quality of medical care. Key words: Quality control circle; Gastric cancer; Chemotherapy; Moderate or severe malnutrition

Remarks on the design and analyses of longitudinal studies for cancer patients with anorexia and weight loss.

Longitudinal data serve an important role in understanding the cancer anorexia weight loss syndrome and in testing interventions to palliative and treat patients who develop this syndrome. The element of time and the interrelatedness of data points define longitudinal data and add to the richness of this type of data. However, longitudinal data can also give rise to non‐random, missing data that can lead to flawed conclusions. This paper discusses these issues and suggests practical considerations for design and analysis of longitudinal cancer anorexia weight loss studies.